Safety, Tolerability, and Pharmacodynamics of IONIS-DGAT2Rx in Adult Patients With Type 2 Diabetes
- Registration Number
- NCT03334214
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief Summary
The purpose is to assess the Safety, Tolerability, and Pharmacodynamics effect of IONIS DGAT2Rx in up to 45 Adult Patients with Type 2 Diabetes.
- Detailed Description
This short-term study will assess changes in hepatic steatosis over a 13-week treatment period in a patient population with higher risk for development of Nonalcoholic fatty liver disease (NAFLD) and Nonalcoholic steatohepatitis (NASH), obese type 2 diabetes mellitus (T2DM) with elevated HbA1c.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 44
- Must have given written informed consent and be able to comply with all study requirements.
- Males or females aged 18-75, inclusive, at the time of Informed Consent.
- Females must be non-pregnant and non-lactating, and either surgically sterile or post- menopausal.
- Males must be surgically sterile, abstinent or using an acceptable contraceptive method.
- Body mass index (BMI) ≥ 27.0 - ≤ 39.0 kilograms per square meter (kg/m^2).
- Diagnosis of Type 2 Diabetes Mellitus with an Hemoglobin A1C (HbA1c) ≥7.3% and ≤9.5% at screening.
- Must have been on a stable dose of Oral Antidiabetic Therapy for a minimum of 3 months prior to Screening.
- ≥ 10% liver fat prior to randomization assessed by MRI-PDFF.
- Stable body weight for at least 3 months before screening.
- Clinically-significant abnormalities in medical history or physical examination.
- Clinically-significant abnormalities in screening laboratory values that would render a participant unsuitable for inclusion, per Sponsor.
- Evidence of uncorrected hypothyroidism or hyperthyroidism results at Screening.
- History of solid organ transplantation or renal dialysis.
- Clinically-significant complications of diabetes.
- Treatment with another Study Drug, biological agent, or device within one-month of screening.
- Known history or evidence of liver disease with a positive test for human immunodeficiency virus (HIV), Hepatitis C virus (HCV), or chronic Hepatitis B virus (HBV), or chronic liver disease other than NASH.
- Recent history of, or current drug or alcohol abuse.
- Current use of concomitant medications known to significantly impact body weight or that may cause liver toxicity, per Investigator
- Use of anticoagulant/Antiplatelet agents unless the dose has been stable for 4 weeks prior to the first dose of study drug]
- Use of non-steroidal anti-inflammatory drug nimesulide or any other drug influencing coagulation (except lose-dose aspirin).
- Use of obeticholic acid or ursodeoxycholic acid
- Considered unsuitable for inclusion by the Principal Investigator
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description IONIS DGAT2Rx IONIS DGAT2Rx Single Dose of DGAT2Rx administered subcutaneously once weekly for 13 weeks Placebo (sterile saline 0.9) Placebo Calculated volume to match active comparator administered subcutaneously once weekly for 13 weeks
- Primary Outcome Measures
Name Time Method Absolute Change in Liver Fat Percentage (Randomized Population) Baseline to Week 15 Absolute change in liver fat percentage as quantified by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) from baseline to post-treatment MRI.
Percentage of Participants With Adverse Events That Were Related to Treatment With IONIS DGAT2Rx Up to 176 days An adverse event (AE) is any unfavorable and unintended sign (including a clinically-significant abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE is considered related to the investigational drug product.
Absolute Change in Liver Fat Percentage (Per Protocol Population) Baseline to Week 15 Absolute change in liver fat percentage as quantified by MRI-PDFF from baseline to post-treatment MRI.
Percentage of Participants With Adverse Events, Graded by Severity, That Were Related to Treatment With IONIS DGAT2Rx Up to 176 days AEs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03, June 2010. Grades: mild - the event is easily tolerated by the participant and does not affect the participant's usual daily activities; moderate - the event causes the participant more discomfort and interrupts the participant's usual daily activities; severe - the event is incapacitating and causes considerable interference with the participant's usual daily activities.
- Secondary Outcome Measures
Name Time Method Percent Change in Liver Volume Baseline to Week 15 Assessed from Baseline MRI to Post-Treatment MRI.
Percent Change in Plasma Lipoprotein Profile Week 15 Percent change in plasma lipoprotein profile (total cholesterol, apolipoprotein B \[ApoB\], high density lipoprotein (HDL), low density lipoprotein cholesterol \[LDL-C\], non-HDL, triglycerides, and very low density lipoproteins \[VLDL\]) from baseline to the average of the post-treatment values assessed 1 and 2 weeks after the last dose (Post-Treatment 1 and Post-Treatment 2 visits).
Percent Change in Liver Fat Percentage Baseline to Week 15 Relative percent change in liver fat percentage from baseline to post-treatment MRI.
Percentage of Participants With ≥ 30% Relative Reduction in Liver Fat Percentage Week 15 Percentage of participants with ≥ 30% relative reduction in liver fat percentage from baseline to post-treatment.
Percent Change in Parameters of Insulin Resistance (IR) Week 14 Percent change in parameters of IR (fasting plasma glucose \[FPG\], homeostatic model assessment - insulin resistance \[HOMA-IR\], and insulin) from baseline to post-treatment.
Absolute Change in Hemoglobin A1C (HbA1C) Week 14 Absolute change in HbA1C from baseline to post-treatment.
Trial Locations
- Locations (1)
Ionis Investigational Site
🇬🇧Nottingham, United Kingdom